Bacterially derived 400 nm particles for encapsulation and cancer cell targeting of chemotherapeutics

MacDiarmid, J. A., Mugridge, N. B., Weiss, J. C., Phillips, L., Burn, A. L., Paulin, R. P., Haasdyk, J. E., Dickson, K. A., Brahmbhatt, V. N., Pattison, S. T., James, A. C., Al Bakri, G., Straw, R. C., Stillman, B., Graham, R. M., Brahmbhatt, H. (2007) Bacterially derived 400 nm particles for encapsulation and cancer cell targeting of chemotherapeutics. Cancer Cell, 11 (5). pp. 431-445. ISSN 1535-6108

URL: http://www.ncbi.nlm.nih.gov/pubmed/17482133
DOI: 10.1016/j.ccr.2007.03.012

Abstract

Systemic administration of chemotherapeutic agents results in indiscriminate drug distribution and severe toxicity. Here we report a technology potentially overcoming these shortcomings through encapsulation and cancer cell-specific targeting of chemotherapeutics in bacterially derived 400 nm minicells. We discovered that minicells can be packaged with therapeutically significant concentrations of chemotherapeutics of differing charge, hydrophobicity, and solubility. Targeting of minicells via bispecific antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release. This affects highly significant tumor growth inhibition and regression in mouse xenografts and case studies of lymphoma in dogs despite administration of minute amounts of drug and antibody; a factor critical for limiting systemic toxicity that should allow the use of complex regimens of combination chemotherapy.

Item Type: Paper
Uncontrolled Keywords: EPIDERMAL-GROWTH-FACTOR ESCHERICHIA-COLI FACTOR RECEPTOR DRUG-DELIVERY EFFLUX PUMPS TUMOR-CELLS IN-VIVO PERMEABILITY DIVISION EFFICACY
Subjects: Investigative techniques and equipment > microspheres
therapies
organism description > bacteria
organism description > bacteria > escherichia coli
CSHL Authors:
Communities: CSHL labs > Stillman lab
Highlight: Stillman, Bruce W.
Depositing User: CSHL Librarian
Date Deposited: 11 Nov 2011 16:06
Last Modified: 20 Jun 2017 16:44
Related URLs:
URI: http://repository.cshl.edu/id/eprint/23088

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